Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial

SPS commentary:

In the trial, with regards to the coprimary endpoints, 13 (59%) on treatment achieved functional independent sitting for ≥30 seconds at 18 month of age study visit vs 0 of 23 in untreated cohort (p<0·0001); also 20 (91%) vs. 6 (26%), respectively, survived free from permanent ventilation at age 14 months (p<0·0001).

According to a commentary, gene therapy is a once in a lifetime treatment because this approach induces antibodies against the viral vector. Preclinical data are encouraging and indicate persistent transgene expression in non-dividing neurons over time. Whether this expression translates into a persistent therapeutic effect in spinal muscular atrophy type 1 remains unknown. Follow-up data are promising but longer-term results are needed, and findings can be affected by concomitant treatment with other disease-modifying therapies. It adds that even with these considerations, gene therapy undoubtedly brings hope for many patients with spinal muscular atrophy and their families. Further data on long-term safety and efficacy, the optimal window for treatment, and the benefits of combining therapies, are eagerly awaited. Such data could support an appropriate use of this promising but expensive therapy and would help to manage treatment-related expectations of patients and clinicians.

Recently NHS England announced a deal with Novartis Gene Therapies, securing onasemnogene abeparvovec (Zolgensma), with reported list price of £1.79m per dose, for NHS patients at a substantial confidential discount, paving the way for NICE to publish draft guidance recommending treatment. The terms of the deal mean that some young children currently outside the NICE recommendation criteria will also be eligible to be considered for treatment by a national multidisciplinary clinical team (MDT). This means as many as 80 babies and young children a year could potentially benefit from this therapy, which contains a replica of the missing gene SMN1, and is given as a single intravenous infusion.

Zolgensma has also been accepted by NHS Scotland for use in patients with 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA type 1, or patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and up to 3 copies of the SMN2 gene.